Skip to main content
Top
Published in: Breast Cancer Research 3/2005

Open Access 01-06-2005 | Research article

Modulation of N-methyl-N-nitrosourea induced mammary tumors in Sprague–Dawley rats by combination of lysine, proline, arginine, ascorbic acid and green tea extract

Authors: M Waheed Roomi, Nusrath W Roomi, Vadim Ivanov, Tatiana Kalinovsky, Aleksandra Niedzwiecki, Matthias Rath

Published in: Breast Cancer Research | Issue 3/2005

Login to get access

Abstract

Introduction

The limited ability of current treatments to control metastasis and the proposed antitumor properties of specific nutrients prompted us to examine the effect of a specific formulation (nutrient supplement [NS]) of lysine, proline, arginine, ascorbic acid, and green tea extract in vivo on the development of N-methyl-N-nitrosourea (MNU)-induced mammary tumors in rats.

Methods

A single intraperitoneal dose of MNU was injected into each of 20 female Sprague–Dawley rats (aged 50 days) to induce tumors. Two weeks after MNU treatment, a time by which the animals had recovered from MNU-induced toxicity, the rats were divided into two groups. Rats in group 1 (n = 10) were fed Purina chow diet, whereas those in group 2 (n = 10) were fed the same diet supplemented with 0.5% NS. After a further 24 weeks, the rats were killed and tumors were excised and processed.

Results

NS reduced the incidence of MNU-induced mammary tumors and the number of tumors by 68.4%, and the tumor burden by 60.5%. The inhibitory effect of NS was also reflected by decreased tumor weight; the tumor weights per rat and per group were decreased by 41% and 78%, respectively. In addition, 30% of the control rats developed ulcerated tumors, in contrast to 10% in the nutrient supplemented rats.

Conclusion

These findings suggest that the specific formulation of lysine, proline, arginine, ascorbic acid, and green tea extract tested significantly reduces the incidence and growth of MNU-induced mammary tumors, and therefore has strong potential as a useful therapeutic regimen for inhibiting breast cancer development.
Appendix
Available only for authorised users
Literature
2.
go back to reference Ali SM, Harvey HA, Lipton A: Metastatic breast cancer: overview of treatment. Clin Orthop. 2003, 132-137. Ali SM, Harvey HA, Lipton A: Metastatic breast cancer: overview of treatment. Clin Orthop. 2003, 132-137.
3.
go back to reference Pantel K, Muller V, Auer M, Nusser N, Harbeck N, Braun S: Detection and clinical implications of early systemic tumor cell dissemination in breast cancer. Clin Cancer Res. 2003, 9: 6326-6334.PubMed Pantel K, Muller V, Auer M, Nusser N, Harbeck N, Braun S: Detection and clinical implications of early systemic tumor cell dissemination in breast cancer. Clin Cancer Res. 2003, 9: 6326-6334.PubMed
4.
go back to reference Rath M, Pauling L: Plasmin-induced proteolysis and the role of apoprotein(a), lysine and synthetic analogs. Orthomol Med. 1992, 7: 17-23. Rath M, Pauling L: Plasmin-induced proteolysis and the role of apoprotein(a), lysine and synthetic analogs. Orthomol Med. 1992, 7: 17-23.
5.
go back to reference Netke SP, Roomi MW, Ivanov V, Niedzwiecki A, Rath M: A specific combination of ascorbic acid, lysine, proline and epigallocatechin gallate inhibits proliferation and extracellular matrix invasion of various human cancer cell lines. Res Commun Pharmacol Toxicol Emerging Drugs. 2003, 2: 37-50. Netke SP, Roomi MW, Ivanov V, Niedzwiecki A, Rath M: A specific combination of ascorbic acid, lysine, proline and epigallocatechin gallate inhibits proliferation and extracellular matrix invasion of various human cancer cell lines. Res Commun Pharmacol Toxicol Emerging Drugs. 2003, 2: 37-50.
6.
go back to reference Russo J, Gusterson BA, Rogers AE, Russo IH, Wellings SR, van Zwieten MJ: Comparative study of human and rat mammary tumorigenesis. Lab Invest. 1990, 62: 244-278.PubMed Russo J, Gusterson BA, Rogers AE, Russo IH, Wellings SR, van Zwieten MJ: Comparative study of human and rat mammary tumorigenesis. Lab Invest. 1990, 62: 244-278.PubMed
7.
go back to reference Welsch CW: Host factors affecting the growth of carciogen-induced rat mammary carcinomas: a review and tribute to Charles Brenton Huggins. Cancer Res. 1985, 45: 3415-3443.PubMed Welsch CW: Host factors affecting the growth of carciogen-induced rat mammary carcinomas: a review and tribute to Charles Brenton Huggins. Cancer Res. 1985, 45: 3415-3443.PubMed
8.
go back to reference Russo J, Russo IH, Rogers AE, Van Zweiten MJ, Gusterson B: Tumors of mammary gland. Pathology of Tumours in Laboratory Animals. Edited by: Turusov V, Mohr U. 1990, Lyon: IARC Scientific Publications, 1: 47-78. Russo J, Russo IH, Rogers AE, Van Zweiten MJ, Gusterson B: Tumors of mammary gland. Pathology of Tumours in Laboratory Animals. Edited by: Turusov V, Mohr U. 1990, Lyon: IARC Scientific Publications, 1: 47-78.
9.
go back to reference Thompson HJ, Mc Ginley JN, Rothhammer K, Singh M: Rapid induction of mammary intraductal proliferation, ductal carcinoma in situ and carcinomas by the injection of sexually immature female rats with 1-methyl-1-nitrosourea. Carcinogenesis. 1995, 16: 2407-2411.CrossRefPubMed Thompson HJ, Mc Ginley JN, Rothhammer K, Singh M: Rapid induction of mammary intraductal proliferation, ductal carcinoma in situ and carcinomas by the injection of sexually immature female rats with 1-methyl-1-nitrosourea. Carcinogenesis. 1995, 16: 2407-2411.CrossRefPubMed
10.
go back to reference Thompson HJ, Adlakha H: Dose-responsive induction of mammary gland carcinomas by the intraperitoneal injection of 1-methyl-I-nitrosourea. Cancer Res. 1991, 51: 3411-3415.PubMed Thompson HJ, Adlakha H: Dose-responsive induction of mammary gland carcinomas by the intraperitoneal injection of 1-methyl-I-nitrosourea. Cancer Res. 1991, 51: 3411-3415.PubMed
11.
go back to reference Roomi MW, Ivanov V, Niedzwiecki A, Rath M: Antitumorigenic activity of Epican Forte in human breast cancer lines MDA MB-231 and MCF-7. Proceedings of the 8th Annual Multidisciplinary Symposium on Breast Disease; 13–16 February 2003. 2003, Jacksonville, FL: University of Florida Health Science Center, #A019- Roomi MW, Ivanov V, Niedzwiecki A, Rath M: Antitumorigenic activity of Epican Forte in human breast cancer lines MDA MB-231 and MCF-7. Proceedings of the 8th Annual Multidisciplinary Symposium on Breast Disease; 13–16 February 2003. 2003, Jacksonville, FL: University of Florida Health Science Center, #A019-
12.
go back to reference Tsao CS: Inhibiting effect of ascorbic acid on the growth of human mammary tumor xenografts. Am J Clin Nutr. 1991, 54 (Suppl 6): 1274S-1280S.PubMed Tsao CS: Inhibiting effect of ascorbic acid on the growth of human mammary tumor xenografts. Am J Clin Nutr. 1991, 54 (Suppl 6): 1274S-1280S.PubMed
13.
go back to reference Anthony HM, Schorah CJ: Severe hypovitaminosis C in lung-cancer patients: the utilization of vitamin C in surgical repair and lymphocyte related host resistance. Br J Cancer. 1982, 46: 354-367.CrossRefPubMedPubMedCentral Anthony HM, Schorah CJ: Severe hypovitaminosis C in lung-cancer patients: the utilization of vitamin C in surgical repair and lymphocyte related host resistance. Br J Cancer. 1982, 46: 354-367.CrossRefPubMedPubMedCentral
14.
go back to reference Nunez C, Ortiz de Apodaca Y, Ruiz A: Ascorbic acid in the plasma and blood cells of women with breast cancer. The effect of consumption of food with an elevated content of this vitamin. Nutr Hosp. 1995, 10: 368-372. Nunez C, Ortiz de Apodaca Y, Ruiz A: Ascorbic acid in the plasma and blood cells of women with breast cancer. The effect of consumption of food with an elevated content of this vitamin. Nutr Hosp. 1995, 10: 368-372.
15.
go back to reference Kurbacher CM, Wagner U, Kolster B, Andreotti PE, Krebs D, Bruckner HW: Ascorbic acid (vitamin C) improves the antineoplastic activity doxorubicin, cisplatin and paclitaxel in human breast carcinoma cells in vitro. Cancer Lett. 1996, 103: 183-189. 10.1016/0304-3835(96)04212-7.CrossRefPubMed Kurbacher CM, Wagner U, Kolster B, Andreotti PE, Krebs D, Bruckner HW: Ascorbic acid (vitamin C) improves the antineoplastic activity doxorubicin, cisplatin and paclitaxel in human breast carcinoma cells in vitro. Cancer Lett. 1996, 103: 183-189. 10.1016/0304-3835(96)04212-7.CrossRefPubMed
16.
go back to reference Valcic S, Timmermann BN, Alberts DS, Wachter GA, Krutzsch M, Wymer J, Guillen JM: Inhibitory effects of six green tea catechins and caffeine on the growth of four selected human tumor cell lines. Anticancer Drugs. 1996, 7: 461-468.CrossRefPubMed Valcic S, Timmermann BN, Alberts DS, Wachter GA, Krutzsch M, Wymer J, Guillen JM: Inhibitory effects of six green tea catechins and caffeine on the growth of four selected human tumor cell lines. Anticancer Drugs. 1996, 7: 461-468.CrossRefPubMed
17.
go back to reference Mukhtar H, Ahmed N: Tea polypheonols: prevention of cancer and optimizing health. Am J Clin Nutr. 2000, 71: 1698-1720. Mukhtar H, Ahmed N: Tea polypheonols: prevention of cancer and optimizing health. Am J Clin Nutr. 2000, 71: 1698-1720.
18.
go back to reference Yang GY, Liao J, Kim K, Yurkow EJ, Yang CS: Inhibition of growth and induction of apoptosis in human cancer cell lines by tea polyphenols. Carcinogenesis. 1998, 19: 611-616. 10.1093/carcin/19.4.611.CrossRefPubMed Yang GY, Liao J, Kim K, Yurkow EJ, Yang CS: Inhibition of growth and induction of apoptosis in human cancer cell lines by tea polyphenols. Carcinogenesis. 1998, 19: 611-616. 10.1093/carcin/19.4.611.CrossRefPubMed
19.
go back to reference Sartippour MR, Heber D, Ma J, Lu Q, Go VL, Nguyen M: Green tea and its catechins inhibit breast cancer xenografts. Nutr Cancer. 2001, 40: 149-156. 10.1207/S15327914NC402_11.CrossRefPubMed Sartippour MR, Heber D, Ma J, Lu Q, Go VL, Nguyen M: Green tea and its catechins inhibit breast cancer xenografts. Nutr Cancer. 2001, 40: 149-156. 10.1207/S15327914NC402_11.CrossRefPubMed
20.
go back to reference Nakachi K, Suemasu K, Suga K, Takeo T, Imai K, Higashi Y: Influence of drinking green tea on breast cancer malignancy among Japanese patients. Jpn J Cancer Res. 1998, 89: 254-261.CrossRefPubMed Nakachi K, Suemasu K, Suga K, Takeo T, Imai K, Higashi Y: Influence of drinking green tea on breast cancer malignancy among Japanese patients. Jpn J Cancer Res. 1998, 89: 254-261.CrossRefPubMed
21.
go back to reference Kavanagh KT, Hafer LJ, Kim DW, Mann KK, Sherr DH, Rogers AE, Sonenshein GE: Green tea extracts decrease carcinogen-induced mammary tumor burden in rats and rate of breast cancer cell proliferation in culture. J Cell Biochem. 2001, 82: 387-398. 10.1002/jcb.1164.CrossRefPubMed Kavanagh KT, Hafer LJ, Kim DW, Mann KK, Sherr DH, Rogers AE, Sonenshein GE: Green tea extracts decrease carcinogen-induced mammary tumor burden in rats and rate of breast cancer cell proliferation in culture. J Cell Biochem. 2001, 82: 387-398. 10.1002/jcb.1164.CrossRefPubMed
Metadata
Title
Modulation of N-methyl-N-nitrosourea induced mammary tumors in Sprague–Dawley rats by combination of lysine, proline, arginine, ascorbic acid and green tea extract
Authors
M Waheed Roomi
Nusrath W Roomi
Vadim Ivanov
Tatiana Kalinovsky
Aleksandra Niedzwiecki
Matthias Rath
Publication date
01-06-2005
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 3/2005
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/bcr989

Other articles of this Issue 3/2005

Breast Cancer Research 3/2005 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine